This research protocol involves an in depth study of the interaction between activated complement fragments and human basophils and mast cells. The substances - histamine, slow reacting substances of anaphylaxis, eosinophil chemotactic factor of anaphylaxis, platelet activating factor, etc. - which are subsequently released from these cells, evoke a wide range of inflammatory responses. It seems probable that this complement-induced mechanism plays a central role in the pathogenesis of many autoimmune and immune-complex hypersensitivity disease states. This project will attempt to purify and characterize the active complement fragment(s) by standard techniques of protein chemistry coupled with biological assays of function. Then, the complement-stimulated secretion of basophils and mast cells will be explored by 1) manipulation of reaction conditions, 2) assaying the biologically-active substances released from the cells, 3) analyzing morphological changes with both light and electron microscopic techniques. The complement-mediated mechanism for triggering these cells will be compared with the allergen-IgE and possible other physiological pathways leading to secretion. These studies should provide a more informed basis for seeking therapeutic control of inflammation induced by complement activation of basophils and mast cells. BIBLIOGRAPHIC REFERENCES: Complement-mediated release of histamine from human leukocytes. J.A. Grant, E. Dupree, A.S. Goldman, D.R. Schultz and A.L. Jackson. Journal of Immunology 114: 1101-1106, March, 1975. Release of chemical mediators from both allergic and non-allergic human leukocytes. J.A. Grant, E. Dupree and A.S. Goldman. International Archives of Allergy and Applied Immunology 49: 111-114, 1975.